This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. An SVV recombinant expressing simian immunodeficiency virus (SIV) antigens was used to vaccinate rhesus macaques in a vaccine/challenge experiment. Ten rhesus monkeys, divided into two groups of five animals each, received subcutaneous and intratracheal inoculations/immunizations with SVV-SIVgag and -SIVenv (Grp1) or SVV-RSVG and -RSVM2 (Gp2) at d0 and at 6weeks. Six months after immunization, all animals were intravenously challenged with 100 TCID50 SIVmac251. Virus loads, were reduced in SVV-SIV vaccinated animals compared with SVV-RSV vaccinated animals at d14 post challenge and continued to increase in significance through 258 days following challenge. Mann Whitney analysis showed significantly lower mean viral loads in Grp1 compared with Gp2 at d14 peak viremia: log 6.8 +/-0.2 and log 7.5 +/-0.4 (p=0.016);and d56 viral set point: log5.3+/-0.5 and log and log6.3+/-0.7 (p=0.03), respectively. Humoral and cellular responses to SIV antigens were documented in this vaccinated group versus the control group. Most intriguing was the production of neutralizing antibodies in the vaccinated animals compared with control animals when tested against H9 grown SIVmac251 but not SIVmac239. We are making efforts to molecularly clone SIVmac251-CX-1 pseudotyped viruses to explain the nature of the neutralization. These results demonstrate that recombinant varicella/SIV vaccines can stimulate humoral, cellular, and neutralizing immune responses against SIVmac antigens in the rhesus macaque and suggest the potential of this SVV-SIV recombinant for protection against simian acquired immunodeficiency syndrome.